Concurrent normative and experimental studies are planned to test the hypothesis that the temporal order of neurogenesis is the initial contributing factor in the establishment of neocortical neural connections. Project #1 is a series of double-labeling studies (HRP histochemistry and 3H-thymidine autoradiography) examining the correlations between the time of origin of neurons projecting to and from the neocortex and the position of their axon terminals. Experiment 1 will focus on the projection from the magnocellular neurons in the basal telencephalon to the neocortex. Experiment 2 will examine the projections from thalamic sensory relay nuclei (medial geniculate, lateral geniculate, ventrobasal nuclei) to subdivisions of their respective sensory cortices (auditory, visual and somesthetic). Experiment 3 will correlate time of origin of pyramidal cells in the motor cortex with their axon terminal locations in the spinal cord. Preliminary studies in the olfactory system and in the spinal cord indicate that older projection neurons have different targets than younger ones. More generally, these experiments are expected to demonstrate that the time of origin of a neuron specifies where its axon will project in the adult nervous system. Project #2 is a comprehensive quantitative analysis of neuron origin in specific areas of the neocortex using cumulative 3H-thymidine autoradiography, which allows the exact determination of the proportion of neurons originating on single embyronic days. Layers II, III, IV, V, VIa and VIb will be quantified separately in the cingulate, retrosplenial, insular, visual, auditory, somatosensory, and motor areas. This project will complete our effort to provide precise timetables of neurogenesis in the entire rat central nervous system.